Xadago Helps to Ease Non-Motor Symptoms Like Apathy, Study Suggests

Known to ease motor fluctuations due to “off periods” in Parkinson’s disease, daily use of Xadago (safinamide) at low dose also appears to significantly decrease such non-motor symptoms as apathy, while improving patients’ sense of motivation and interest over six months, a real-life study reported.

The study, “Effects of safinamide on non-motor, cognitive, and behavioral symptoms in fluctuating Parkinson’s disease patients: a prospective longitudinal study,” was published in the journal Neurological Sciences.

Levodopa is a primary Parkinson’s medication, used to treat motor symptoms. It is converted into dopamine in the brain, the signaling molecule that relays electric signals between nerve cells, which is lacking in people with the condition. 

Over its long-term use, however, levodopa leads to debilitating fluctuations between normal motor function, known as “on periods,” and poorer function or “off periods.”

Xadago, developed by Newron Pharmaceuticals and marketed in the U.S. by Supernus, is an approved, daily oral add-on therapy to levodopa, designed to improve motor function in patients experiencing “off episodes.” It works by blocking the enzyme monoamine oxidase B that breaks down dopamine and prevents dopamine uptake. Xadago also works to suppress the excessive release of another signaling molecule, glutamate.

Most clinical trials evaluating Xadago have focused on motor function as a primary outcome. Secondary trial outcomes also indicated that the medication supported a better quality of life, as well as easing non-motor symptoms such as pain, sleep, and mood. 

However, no study to date has tested the impact of Xadago solely on a broad spectrum of non-motor, cognitive, and behavioral-related features in adults with Parkinson’s. 

“Thus, the aim of the present study is to investigate, by means of several [Parkinson’s]-specific and validated scales, whether [Xadago] may improve these symptoms over a 6-month treatment period in a [group] of mid-stage [Parkinson’s] patients experiencing motor fluctuations,” researchers at the University of Campania Luigi Vanvitelli in Italy wrote. 

Selected patients had Parkinson’s onset after age 40, reported than 1.5 “off episode” motor fluctuations each day, and received regular dopamine-related treatments over the previous 30 days. The study excluded those with previous Xadago treatment, Parkinson’s-associated dementia, chronic depression, or a history of psychiatric illness.

In total, 11 men and nine women with Parkinson’s, with a mean age of 63.8, were enrolled. Seven out of 20 participants had uncontrolled involuntary movements (dyskinesia) combined with other motor fluctuations.

Compared with initial (baseline) measures, daily treatment with Xadago at 50 mg significantly decreased the total daily hours with “off episodes” from a mean of 1.6 per day to 1.0 per day after six months. These findings were consistent with those previous clinical trials.

No significant changes were seen with dyskinesia and dyskinesia severity, as assessed by the Unified Parkinson’s Disease Rating Scale (UPDRS IV) and the Abnormal Involuntary Movements Scale (AIMS). 

Overall, non-motor symptoms decreased significantly based on the Non-Motor Symptom Scale (NMSS), relative to those recorded before treatment. 

Out of the 30 NMSS sub-domains, Xadago significantly improved motivation, as well as the “interest” domain, which measures whether the patient has lost interest in their surroundings or lost interest in activities or the willingness to start new activities. It also significantly eased urine frequency.

A significant decrease was also reported in the Scales for Outcomes in Parkinson’s Disease–Autonomic (SCOPA-AUT) scores, which measures autonomic symptoms related to digestion, and urinary, cardiovascular, body temperature regulation, as well as eye pupil movement and sexual function. 

Fatigue significantly lessened after Xadago treatment at follow-up, as measured by the Parkinson’s disease Fatigue Scale (PFS). Apathy symptoms also significantly eased, as assessed with the Apathy Evaluation Scale (AES), but no change with treatment was evident in cognitive abilities. 

Higher modified Hoehn and Yahr (mH&Y) stage scores at baseline — a measure of Parkinson’s progression, in which higher scores indicated greater progression — correlated with lesser improvements in anxiety, cognition, and sleepiness symptoms over time. 

Lesser improvement in motor outcomes (UPDRS III scores) over time also correlated with lesser improvements in depressive, anxiety, fatigue, or apathy symptoms over time. No other correlations were found between motor and non-motor symptoms or cognitive and behavioral outcomes after six months of treatment with Xadago.

Xadago at the dose of 50 mg/daily was safe and well-tolerated, with no major or unexpected safety concerns reported. 

“In conclusion, the consistent significant and clinically relevant improvement over [six] months in motor outcome confirms the effectiveness of [Xadago] 50 mg in fluctuating patients with [Parkinson’s disease],” the researchers wrote.

“Moreover, we have demonstrated that non-motor and behavioral [Parkinson’s disease]-related symptoms may benefit from [Xadago] treatment, even at the lowest available dose of 50 mg,” they added. 

“Future studies with longer follow-up periods and a larger number of patients are needed to confirm and possibly expand our results.”